The regulation of metabolism in the animal involves the interaction of hormonal influences on the mobilization and utilization of the various metabolic fuels. The effect of a given hormone may be influenced by the hormonal and metabolic response that it evokes. The present study is concerned with the regulation of production and utilization of glucose, free fatty acids and glycerol, and with the actions and interactions of the various pituitary (growth hormone, prolactin), adrenal (cortisol, epinephrine) and pancreatic (glucagon, insulin) hormones on these metabolic processes. Measurements of production and utilization of specific metabolic fuels will be carried out in trained dogs, using infusions of glucose-3-H3, palmitate-14C and glucerol-U-14C. Evaluation of hormonal interactions will involve detection of hormones (insulin, glucagon, cortisol, growth hormone) in the plasma, using radioimmunoassay, the use of appropriate blocking agents (alpha and beta adrenergic blockers) as well as use of agents which have selective inhibitory effects on hormone secretion (somatostatin, diazoxide). Metabolic adaptations in response to hormones may alter the usual effect of individual hormones. The present studies will seek to identify such adaptation and to evaluate their influence on hormonal responses by experimentally altering the metabolic substrate through dietary manipulations. The various hormonal and metabolic interrelations will be studied in normal animals as well as in animals with experimentally-induced metabolic disorders, eg. diabetes mellitus.